The cellular src gene product displays a unique pattern of expression in neuronal cells that differs qualitatively and quantitatively from that found in other cell (designated pp60 c- src(+)) which contains a 6-amino acid insert within the amino- terminal region of the protein. This insert appears to be a consequence of a unique pattern of c-src mRNA splicing in neurons since c-src cDNA clones isolated from chicken and mouse brain cDNA libraries contain an 18-nucleotide insert located between the exons 3 and 4. The finding that neurons specifically express high levels of an altered form of pp60 c-src, and the evidence that tyrosine kinases are involved in pp60 c-src may play a role in regulating neuronal cell function. This proposal describes plans to further characterize the functional activity of this unique form of pp60 c-src and its localization in neural tissues. We also will examine how expression to isolate and characterize cellular proteins that might interact with pp60 c-src(4) to regulate its functional activity. These experiments should provide clues to the function of pp60 c-src which serves as a model protein for the src-family of proto-oncogene products that are associated exclusively with the cytoplasmic face of he plasma membrane, and thus cannot function directly as receptors for peptide hormones.